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Tytuł:
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Flavonoids potentiated anticancer activity of cisplatin in non-small cell lung cancer cells in vitro by inhibiting histone deacetylases.
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Autorzy:
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Yan W; School of Pharmacy, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
Wu THY; School of Pharmacy, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
Leung SSY; School of Pharmacy, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
To KKW; School of Pharmacy, The Chinese University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: .
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Źródło:
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Life sciences [Life Sci] 2020 Oct 01; Vol. 258, pp. 118211. Date of Electronic Publication: 2020 Aug 06.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: <2008->: Amsterdam : Elsevier
Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press.
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MeSH Terms:
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Antineoplastic Agents/*administration & dosage
Carcinoma, Non-Small-Cell Lung/*enzymology
Cisplatin/*administration & dosage
Flavonoids/*administration & dosage
Histone Deacetylase Inhibitors/*administration & dosage
Lung Neoplasms/*enzymology
A549 Cells ; Antineoplastic Agents/chemistry ; Apigenin/administration & dosage ; Apigenin/chemistry ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Survival/drug effects ; Cell Survival/physiology ; Cisplatin/chemistry ; Dose-Response Relationship, Drug ; Drug Synergism ; Flavonoids/chemistry ; Histone Deacetylase Inhibitors/chemistry ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/pathology
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Contributed Indexing:
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Keywords: Apigenin; Cisplatin; Histone deacetylases; Non-small cell lung cancer
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Substance Nomenclature:
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0 (Antineoplastic Agents)
0 (Flavonoids)
0 (Histone Deacetylase Inhibitors)
7V515PI7F6 (Apigenin)
Q20Q21Q62J (Cisplatin)
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Entry Date(s):
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Date Created: 20200810 Date Completed: 20200930 Latest Revision: 20200930
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Update Code:
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20240105
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DOI:
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10.1016/j.lfs.2020.118211
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PMID:
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32768576
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Aims: Cisplatin is the mainstay of first-line treatment for advanced non-small cell lung cancer (NSCLC). Accumulating evidence suggests that flavonoids inhibit histone deacetylase (HDAC) to mediate their anticancer effect in various cancer types. The study was conducted to investigate the inhibition of HDAC and the modulation of apoptotic and cell cycle regulatory genes by selected flavonoids to potentiate the anticancer effect of cisplatin.
Main Methods: Combinations of cisplatin and selected flavonoids were investigated in three NSCLC cell lines (A549, H460, and H1299). Sulforhodamine B assay was used to evaluate cytotoxicity of drug combinations. Western blot analysis was conducted to evaluate histone acetylation. Flow cytometric assays were used to investigate the apoptotic and cell cycle effect. Chromatin immunoprecipitation assay was performed to elucidate the binding of transcription factors to promoters of selected apoptotic and cell cycle regulatory genes.
Key Findings: Apigenin was found to exhibit the strongest HDAC inhibitory effect among all flavonoids tested. Cisplatin-apigenin combination was shown to produce significantly more S phase prolongation and G2/M cell cycle arrest, and apoptosis compared with cisplatin or apigenin alone, by inducing p21 and PUMA, respectively. More pronounced effect was observed in p53-proficient than p53-null NSCLC cells. Mechanistically, apigenin was found to reduce the binding of HDAC1 but increase the association of RNA polymerase II and Sp1 to p21 and PUMA promoters.
Significance: Our findings provide a better insight about the mechanism contributing to the HDAC inhibitory effect of apigenin to potentiate anticancer effect of cisplatin by inducing apoptosis and cell cycle arrest.
Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
